Many antitumor and antiviral agents exert their therapeutic and toxic effects by creating structural or conformational changes in DNA. Mutagens and chemical carcinogens appear to be involved in similar interactions. The common event to these phenomena is the interaction of a small molecule with DNA. The experiments described in this proposal are designed to identify specific sites in DNA which bind antitumor drugs and carcinogens. We propose to apply this information to the use of drugs as molecular probes of chromatin structure. Recombinant DNA techniques will be employed to explore the relationship between drug-induced damage to DNA and mutagenesis. Finally, we propose an extension of our ongoing work on the mechanism of action of bleomycin. The long term goals of this research are aimed at elucidating the molecular basis of drug- and carcinogen-interactions with DNA. Studies of this type should enhance greatly our understanding of carcinostatic and carcinogenic mechanisms. In addition, structure-activcity relationships will be established that can ultimately be applied in the rational design of drugs that modulate the biological effects of DNA.